Effects of Metformin on Clinical Outcomes After Acute Ischemic Stroke in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

Objective: This study investigated the effects of metformin on clinical outcomes after acute ischemic stroke in patients with type 2 diabetes mellitus (T2DM). Methods: PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched for relevant English articles published from database inception to 6 April 2026. Moreover, the reference lists of eligible articles were searched. Studies were included if they focused on patients with T2DM and acute ischemic stroke, indicated whether the patients used metformin before stroke onset, and reported the patients’ modified Rankin Scale (mRS) scores after stroke onset. Studies lacking adequate outcome data were excluded. Two reviewers independently extracted relevant data—for example, study details, clinicodemographic characteristics, and poststroke outcomes (mRS scores, National Institutes of Health Stroke Scale [NIHSS] scores, symptomatic intracranial hemorrhage [sICH], and mortality). A senior reviewer was consulted in cases of between-reviewer disagreements. The primary outcome was poststroke mRS score (functional outcome), and the secondary outcomes were poststroke NIHSS scores (neurological severity), sICH, and mortality. Results: Eleven studies met the inclusion criteria. Most studies reported better functional outcomes (mRS scores) and lower NIHSS scores for metformin users than for nonusers. Some studies indicated reduced rates of sICH and mortality among metformin users than among nonusers. Sensitivity analyses generally supported the benefits of metformin. Caution should be exercised when interpreting these findings because the results might have been influenced by variations in study designs, stroke classifications, and renal function reporting. Conclusions: In patients with T2DM, metformin may reduce stroke severity and improve poststroke functional outcomes. To the best of our knowledge, this meta-analysis is the first to investigate the association between metformin use and neurological severity, estimate adjusted ORs for favorable functional outcomes, and highlight publication bias on this topic.